Mechanisms of endothelial cell dysfunction in cystic fibrosis

Although cystic fibrosis (CF) patients exhibit signs of endothelial perturbation, the functions of the cystic fibrosis conductance regulator (CFTR) in vascular endothelial cells (EC) are poorly defined. We sought to uncover biological activities of endothelial CFTR, relevant for vascular homeostasis and inflammation. We examined cells from human umbilical cords (HUVEC) and pulmonary artery isolated from non-cystic fibrosis (PAEC) and CF human lungs (CF-PAEC), under static conditions or physiological shear. CFTR activity, clearly detected in HUVEC and PAEC, was markedly reduced in CF-PAEC. CFTR blockade increased endothelial permeability to macromolecules and reduced trans‑endothelial electrical resistance (TEER). Consistent with this, CF-PAEC displayed lower TEER compared to PAEC. Under shear, CFTR blockade reduced VE-cadherin and p120 catenin membrane expression and triggered the formation of paxillin- and vinculin-enriched membrane blebs that evolved in shrinking of the cell body and disruption of cell-cell contacts. These changes were accompanied by enhanced release of microvesicles, which displayed reduced capability to stimulate proliferation in recipient EC. CFTR blockade also suppressed insulin-induced NO generation by EC, likely by inhibiting eNOS and AKT phosphorylation, whereas it enhanced IL-8 release. Remarkably, phosphodiesterase inhibitors in combination with a β2 adrenergic receptor agonist corrected functional and morphological changes triggered by CFTR dysfunction in EC. Our results uncover regulatory functions of CFTR in EC, suggesting a physiological role of CFTR in the maintenance EC homeostasis and its involvement in pathogenetic aspects of CF. Moreover, our findings open avenues for novel pharmacology to control endothelial dysfunction and its consequences in CF

Local discrimination of orbital angular momentum in entangled states

We address the use of a calcite crystal-based local detector to the discrimination of orbital angular momentum of quantum radiation produced by parametric down conversion. We demonstrate that a discrimination can be obtained exploiting the introduction of a fine and controlled spatial shift between two replicas of the state in the crystals. We believe that this technology could be used for future development of long-distance quantum communication techniques, where information encoding is based on orbital angular momentum

Non-invasive brain stimulation techniques for the improvement of upper limb motor function and performance in activities of daily living after stroke: a systematic review and network meta-analysis

Objective: To compare the efficacy of non-invasive brain stimulation (NiBS) such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), and transcutaneous vagus nerve stimulation (taVNS) in upper limb stroke rehabilitation. Data sources: PubMed, Web of Science, and Cochrane databases were searched from January 2010 to June 2022. Data selection: Randomized controlled trials (RCT's) assessing the effects of "tDCS", "rTMS", "TBS", or "taVNS" on upper limb motor function and performance in activities of daily livings (ADLs) after stroke. Data extraction: Data were extracted by 2 independent reviewers. Risk of bias were was evaluated with the Cochrane Risk of Bias tool. Data synthesis: 87 RCTs with 3750 participants were included. Pairwise meta-analysis showed that all NiBS except continuous TBS (cTBS) and cathodal tDCS were significantly more efficacious than sham stimulation for motor function (Standard Meand Differerence (SMD) range 0.42 to 1.20) whereas taVNS, anodal tDCS, and both low and high frequency rTMS were significantly more efficacious than sham stimulation for ADLs (SMD range 0.54 to 0.99). NMA showed that taVNS was more effective than cTBS (SMD:1.00;95%CI(0.02 to 2.02), cathodal tDCS (SMD:1.07;95%CI(0.21 to 1.92) and Physical rehabilitation alone (SMD:1.46;95%CI(0.59 to 2.33)) for improving motor function. P-score found that taVNS is best ranked treatment in improving motor function (SMD: 1.20;95%CI(0.46 to 1.95) and ADLs (SMD:1.20;95%CI(0.45 to 1.94) after stroke. After taVNS, excitatory stimulation protocols (intermittent TBS, anodal tDCS and HF-rTMS) are most effective in improving motor function and ADLs after acute/sub-acute (SMD range 0.53 to 1.63) and chronic stroke (SMD range 0.39 to 1.16). Conclusions: Evidence suggests that excitatory stimulation protocols are the most promising intervention in improving upper limb motor function and performance in ADLs. taVNS appeared to be a promising intervention for stroke patients, but further large RCTs are required to confirm its relative superiority

A novel STK11 gene mutation (c.388dupG, p.Glu130Glyfs∗33) in a Peutz-Jeghers family and evidence of higher gastric cancer susceptibility associated with alterations in STK11 region aa 107-170

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Phylogeny-and abundance-based metrics allow for the consistent comparison of core gut microbiome diversity indices across host species

The filtering of gut microbial datasets to retain high prevalence taxa is often performed to identify a common core gut microbiome that may be important for host biological functions. However, prevalence thresholds used to identify a common core are highly variable, and it remains unclear how they affect diversity estimates and whether insights stemming from core microbiomes are comparable across studies. We hypothesized that if macroecological patterns in gut microbiome prevalence and abundance are similar across host species, then we would expect that increasing prevalence thresholds would yield similar changes to alpha diversity and beta dissimilarity scores across host species datasets. We analyzed eight gut microbiome datasets based on 16S rRNA gene amplicon sequencing and collected from different host species to (1) compare macroecological patterns across datasets, including amplicon sequence variant (ASV) detection rate with sequencing depth and sample size, occupancy-abundance curves, and rank-abundance curves; (2) test whether increasing prevalence thresholds generate universal or host-species specific effects on alpha and beta diversity scores; and (3) test whether diversity scores from prevalence-filtered core communities correlate with unfiltered data. We found that gut microbiomes collected from diverse hosts demonstrated similar ASV detection rates with sequencing depth, required different sample sizes to sufficiently capture rare ASVs across the host population. This suggests that sample size rather than sequencing depth tends to limit the ability of studies to detect rare ASVs across the host population. Despite differences in the distribution and detection of rare ASVs, microbiomes exhibited similar occupancy-abundance and rank-abundance curves. Consequently, increasing prevalence thresholds generated remarkably similar trends in standardized alpha diversity and beta dissimilarity across species datasets until high thresholds above 70%. At this point, diversity scores tended to become unpredictable for some diversity measures. Moreover, high prevalence Frontiers in Microbiology. Filtering Effects on Core Microbiome thresholds tended to generate diversity scores that correlated poorly with the original unfiltered data. Overall, we recommend that high prevalence thresholds over 70% are avoided, and promote the use of diversity measures that account for phylogeny and abundance (Balance-weighted phylogenetic diversity and Weighted Unifrac for alpha and beta diversity, respectively), because we show that these measures are insensitive to prevalence filtering and therefore allow for the consistent comparison of core gut microbiomes across studies without the need for prevalence filtering.publishedVersio

Employing Microwave Graphene Field Effect Transistors for Infrared Radiation Detection

In this work, we investigate the possibility of employing graphene field effect transistors, specifically designed for microwave applications, as infrared detectors for telecom applications. Our devices have been fabricated on a sapphire substrate employing CVDgrown transferred graphene. The roles of both the gate dielectric and the DC bias conditions have been evaluated in order to maximize the infrared generated signal through an experimental investigation of the signal-to-noise ratio dependence on the transistor operating point

Splitting of multiple hydrogen molecules by bioinspired diniobium metal complexes: a DFT study

Splitting of molecular hydrogen (H2) into bridging and terminal hydrides is a common step in transition metal chemistry. Herein, we propose a novel organometallic platform for cleavage of multiple H2 molecules, which combines metal centers capable of stabilizing multiple oxidation states, and ligands bearing positioned pendant basic groups. Using quantum chemical modeling, we show that low-valent, early transition metal diniobium(II) complexes with diphosphine ligands featuring pendant amines can favorably uptake up to 8 hydrogen atoms, and that the energetics are favored by the formation of intramolecular dihydrogen bonds. This result suggests new possible strategies for the development of hydrogen scavenger molecules that are able to perform reversible splitting of multiple H2 molecules

Bdnf-Nrf-2 crosstalk and emotional behavior are disrupted in a sex-dependent fashion in adolescent mice exposed to maternal stress or maternal obesity

Maternal obesity has been recognized as a stressor affecting the developing fetal brain, leading to long-term negative outcomes comparable to those resulting from maternal psychological stress, although the mechanisms have not been completely elucidated. In this study, we tested the hypothesis that adverse prenatal conditions as diverse as maternal stress and maternal obesity might affect emotional regulation and stress response in the offspring through common pathways, with a main focus on oxidative stress and neuroplasticity. We contrasted and compared adolescent male and female offspring in two mouse models of maternal psychophysical stress (restraint during pregnancy - PNS) and maternal obesity (high-fat diet before and during gestation - mHFD) by combining behavioral assays, evaluation of the hypothalamic-pituitary-adrenal (HPA) axis reactivity, immunohistochemistry and gene expression analysis of selected markers of neuronal function and neuroinflammation in the hippocampus, a key region involved in stress appraisal. Prenatal administration of the antioxidant N-acetyl-cysteine (NAC) was used as a strategy to protect fetal neurodevelopment from the negative effects of PNS and mHFD. Our findings show that these two stressors produce overlapping effects, reducing brain anti-oxidant defenses (Nrf-2) and leading to sex-dependent impairments of hippocampal Bdnf expression and alterations of the emotional behavior and HPA axis functionality. Prenatal NAC administration, by restoring the redox balance, was able to exert long-term protective effects on brain development, suggesting that the modulation of redox pathways might be an effective strategy to target common shared mechanisms between different adverse prenatal conditions